Lynn M Opdenaker, Ryan Kowash, Gabriel Masters, Bruce M Boman, Tao Zhang, Shirin R Modarai
{"title":"Increased Musashi-2 and Decreased NUMB Protein Levels Observed in Human Colorectal Cancer are reverted to Normal Levels by ATRA-Induced Cell Differentiation.","authors":"Lynn M Opdenaker, Ryan Kowash, Gabriel Masters, Bruce M Boman, Tao Zhang, Shirin R Modarai","doi":"10.33140/ijcrt/03/02/00003","DOIUrl":"https://doi.org/10.33140/ijcrt/03/02/00003","url":null,"abstract":"<p><strong>Background: </strong>Musashi stem cell (SC) proteins (MSI-1 & MSI-2) are known to become over expressed during colorectal tumorigenesis in humans and mice. MSI-1 overexpression induces tumorigenesis through Notch activation via inactivation of NUMB. Previous studies also show that MSI-2 overexpression in mice induces intestinal tumorigenesis but the mechanism is independent of NUMB. However, whether the MSI-2/NUMB pathway contributes to colorectal cancer (CRC) development in humans is still undetermined.</p><p><strong>Methods: </strong>We evaluated expression of MSI-2 and NUMB proteins in matched normal and CRC patient samples, as well as in human CRC cell lines. We also determined whether induction of cellular differentiation by all-trans retinoic acid (ATRA) influences MSI-2 and NUMB expression.</p><p><strong>Results: </strong>Analysis of matched patient tissue samples and CRC cell lines showed that MSI-2 protein expression is significantly increased and NUMB expression is decreased in CRCs compared to the normal colonic tissue. Immunostaining of normal and adenomatous colonic epithelium revealed that MSI-1+ andMSI-2+ SCs reside in the SC niche and they become overpopulated during colon tumorigenesis. Moreover, promoting cellular differentiation by ATRA reduces MSI-2 protein levels, while increasing NUMB protein levels in human CRC cell lines.</p><p><strong>Conclusions: </strong>MSI-2/NUMB protein expression is altered during colon tumorigenesis, and indicates that MSI-2/NUMB signaling in human colonic stem cells is closely linked to normal colonic epithelial homeostasis.</p><p><strong>Implications: </strong>The ability to normalize MSI-2/NUMB signaling by inducing differentiation of cancer SCs suggests a novel therapeutic approach for CRC treatment.</p>","PeriodicalId":93106,"journal":{"name":"International journal of cancer research & therapy","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38427713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Introduction of a Portable and Non-Invasive Technology for Hand and Foot Cooling: a Preclinical Feasibility Study","authors":"","doi":"10.33140/ijcrt.06.02.05","DOIUrl":"https://doi.org/10.33140/ijcrt.06.02.05","url":null,"abstract":"Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is caused by damage to neural structures in distal limbs. CIPN can lead to reduced dose or cessation of chemotherapy. Cryotherapy has shown to be effective in reducing or preventing CIPN in the hands/feet. However, when using ice bath or ice gloves/socks there is no way to maintain the targeted temperature and prevent ice from melting. Also, patients have difficulty tolerating the freezing temperatures over long periods of chemotherapy. The aim of this study was to test the cooling performance of a recently developed non-invasive system that can ultimately replace current cooling methods. Materials and Methods: COOLPREVENT circulates cold water at tolerable temperatures into malleable gloves/socks that does not require replacing of melted ice. We administered a cooling protocol via COOLPREVENT on three healthy subjects for 60 minutes. Immediately before and after cooling, skin temperature in the hands and feet were measured. Level of discomfort was also recorded during the cooling process. Results: Results showed that COOLPREVENT reduces skin temperature by 14.5±3.8°C and 10.7±1.7°C in the hands and feet, respectively within 60 minutes without significant discomfort. Conclusion: Although our study is limited by the small number of subjects and participation of healthy individuals, but we can conclude that COOLPREVENT can be a safe and appropriate method for hand and foot cooling in a uniform manner. We hope that these preliminary findings can pave the way to designing clinical trials we plan to conduct in the near future.","PeriodicalId":93106,"journal":{"name":"International journal of cancer research & therapy","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69508317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Can we cure our patients in palliative care?","authors":"","doi":"10.33140/ijcrt.06.02.06","DOIUrl":"https://doi.org/10.33140/ijcrt.06.02.06","url":null,"abstract":"With the publication of Flexner report in 1910 and implementation in 1913, with the Rockefeller Foundation and Carnegie Foundation behind it, all medical schools on the main continents of the planet (America, Europe, and Asia) had to adapt to follow the new model of a so-called scientific school. Schools that did not meet the Flexner criteria had to be closed, such as those teaching herbal medicine, naturopathy, homeopathy, etc and only 20% of the schools maintain working. The history of medicine in USA was written by King (1984) in the article entitled XX. The Flexner Report of 1910 [1].","PeriodicalId":93106,"journal":{"name":"International journal of cancer research & therapy","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69508325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Consensus guidelines are required for the peri-operative nutritional assessment and management of patients who undergo surgical resection for suspected pancreatic cancer","authors":"","doi":"10.33140/ijcrt.06.02.04","DOIUrl":"https://doi.org/10.33140/ijcrt.06.02.04","url":null,"abstract":"Surgical resection remains the only treatment option for patients with pancreatic cancer who wish to achieve long-term survival. Despite recent advances, this is associated with considerable morbidity and mortality. Surgical candidates are frequently malnourished, and this is known to negatively affect outcomes. Despite this, the nutritional assessment and management of pancreatic cancer patients remains highly variable and there is no consensus. We argue that a specialist nutrition professional should be involved pre-operatively to optimise outcomes and to identify patients who require additional support. Micronutrient deficiencies are common amongst surgical candidates; it is unknown whether this affects outcomes. Furthermore, it is unknown if correcting deficiencies is of benefit. Robust studies are required to investigate this. Finally, there is limited evidence to support the use of prehabilitation in pancreatic surgery, but this is starting to emerge. The present short communication aims to review the recent literature and comment on the above issues.","PeriodicalId":93106,"journal":{"name":"International journal of cancer research & therapy","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69508262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}